Obscure brain region sheds light on addiction

Our brains are wired to retain information that relates to the context in which highly significant events occurred, such as our first kiss for example. This mechanism also underlies drug addiction and is the reason why hanging out in an environment or with people associated with memories of drug use often leads to relapse.

How our brains create this strong association, however, is less clear. Now, new research from The Hebrew University of Jerusalem shows that a relatively obscure brain region known as the claustrum plays a significant role in making these connections. The study has been published in the journal Current Biology.

The researchers’ findings fit the idea of ‘incentive salience’; the process that determines the desirability of an otherwise neutral stimulus. For example, the facade of a lolly shop becomes very attractive to children after repeated associations with the rewarding treats that lie within. Taking a closer look at how context becomes associated with cocaine, the researchers found a group of neurons within the claustrum that lit up during cocaine use. Further, these neurons are pivotal in the formation of an incentive salience that links context with the pleasure of cocaine.

To determine when and how the claustrum participates in incentive salience, the team employed a conditioned-place preference (CPP) test for a group of lab mice, in which they administered cocaine to the mice and placed them in an area with distinctive flooring (rugged) and wall patterns (dots) as the drug started to kick in. After a few instances of this, when placed in a room where the mice could choose either to hang out in a region similar to the one paired with cocaine (rugged floors and dots wall) or a neutral area (smooth floor and striped walls), the mice would quickly congregate in the area where their drug high had played out.

To test the claustrum’s involvement in how a context becomes associated with a given reward, the team observed the changes in mice behaviour when they inhibited these claustral neurons. They found that the inhibition of these neurons inhibited the mice’s behavioural responses to cocaine, meaning they no longer preferred hanging out in the cocaine-paired environment. On the other hand, activating these neurons — even in the absence of any cocaine — caused the mice to develop a preference for this context.

Importantly, the team found that the activity of the claustrum was not necessary for retrieval of the cocaine memory. Once the mice had been placed in a cocaine-paired context several times to enjoy their cocaine high, the memory for this context was encoded and inhibition of the claustrum had no effect on their preference for the cocaine-paired context.

“These findings boosted our confidence that the claustrum is indeed integral to incentive salience, heightening the awareness of the mouse to the context in which it experienced the drug high,” said Professor Ami Citri, who co-led the research.

The study thus has implications towards a better understanding of the nature of addiction and the importance of breaking contextual cues before they develop. Co-leader Anna Terem concluded, “We hope this knowledge will lead to the development of new diagnostic tools to identify populations susceptible to addiction, as well as new therapeutic approaches.”

Image credit: ©1dbrf10/Dollar Photo Club

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